Study of oxidative stress, anti-oxidant status and their relation to apoptosis in acute lymphoblastic leukemia

ABSTRACT

Acute lymphoblastic leukemias [ALL] are the most common forms of childhood cancer. The exact etiology of acute leukemia is multifactorial. Oxidative stress and apoptosis are among the most important in the pathogenesis of ALL. The aim of the present study is to study the status of oxidative stress [oxygen free radicals and the anti-oxidant activity] in children with acute lymphoblastic leukemia [ALL] and its relation to apoptotic pathway by studying Fas receptor/Fas ligand [FasL] and Bcl-2. The study is conducted on 20 children suffering from acute lymphoblastic leukemia, and 10 age and sex-matched healthy children as a control group. Estimation of plasma levels of albumin, uric acid and bilirubin [as examples of anti-oxidants], anti-oxidant enzyme superoxide dismutase [SOD], Malonyldialdehyde [MDA] which reflects the extent of oxidative stress is performed. Also soluble Fas-L and Bcl-2 are assayed [to reflect apoptosis]. Levels of malonyldialdehyde are found to be elevated and SOD activity is reduced which reflects oxidative stress in ALL patients. Also ALL patients showed elevated levels of sFasL and Bcl-2. From the present study, it can be concluded that patients suffering from acute lymphoblastic leukemia are subjected to greater oxidative stress than normal children. This oxidative stress may be due to their greater exposure to oxygen free radicals or due to defective anti-oxidant defense mechanisms in these patients. It is also found that ALL is associated with defect in apoptosis as evidenced by increased expression of Bcl-2 [anti-apoptotic] and increased sFas-L, which opposes the Fas/CD95 pathway [pro-apoptotic]. This anti-apoptosis may be induced by increased oxidative stress in these ALL patients